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Science (New York, N.Y.) Oct 2023Epistasis between genes is traditionally studied with mutations that eliminate protein activity, but most natural genetic variation is in cis-regulatory DNA and...
Epistasis between genes is traditionally studied with mutations that eliminate protein activity, but most natural genetic variation is in cis-regulatory DNA and influences gene expression and function quantitatively. In this study, we used natural and engineered cis-regulatory alleles in a plant stem-cell circuit to systematically evaluate epistatic relationships controlling tomato fruit size. Combining a promoter allelic series with two other loci, we collected over 30,000 phenotypic data points from 46 genotypes to quantify how allele strength transforms epistasis. We revealed a saturating dose-dependent relationship but also allele-specific idiosyncratic interactions, including between alleles driving a step change in fruit size during domestication. Our approach and findings expose an underexplored dimension of epistasis, in which cis-regulatory allelic diversity within gene regulatory networks elicits nonlinear, unpredictable interactions that shape phenotypes.
Topics: Alleles; Epistasis, Genetic; Fruit; Genetic Variation; Genotype; Phenotype; Solanum lycopersicum; Gene Expression Regulation, Plant; Promoter Regions, Genetic; Gene Dosage
PubMed: 37856609
DOI: 10.1126/science.adi5222 -
Nature Oct 2023Spatially charting molecular cell types at single-cell resolution across the 3D volume is critical for illustrating the molecular basis of brain anatomy and functions....
Spatially charting molecular cell types at single-cell resolution across the 3D volume is critical for illustrating the molecular basis of brain anatomy and functions. Single-cell RNA sequencing has profiled molecular cell types in the mouse brain, but cannot capture their spatial organization. Here we used an in situ sequencing method, STARmap PLUS, to profile 1,022 genes in 3D at a voxel size of 194 × 194 × 345 nm, mapping 1.09 million high-quality cells across the adult mouse brain and spinal cord. We developed computational pipelines to segment, cluster and annotate 230 molecular cell types by single-cell gene expression and 106 molecular tissue regions by spatial niche gene expression. Joint analysis of molecular cell types and molecular tissue regions enabled a systematic molecular spatial cell-type nomenclature and identification of tissue architectures that were undefined in established brain anatomy. To create a transcriptome-wide spatial atlas, we integrated STARmap PLUS measurements with a published single-cell RNA-sequencing atlas, imputing single-cell expression profiles of 11,844 genes. Finally, we delineated viral tropisms of a brain-wide transgene delivery tool, AAV-PHP.eB. Together, this annotated dataset provides a single-cell resource that integrates the molecular spatial atlas, brain anatomy and the accessibility to genetic manipulation of the mammalian central nervous system.
Topics: Animals; Mice; Brain; Central Nervous System; Single-Cell Analysis; Spinal Cord; Transcriptome; Single-Cell Gene Expression Analysis; Viral Tropism; Datasets as Topic; Transgenes; Imaging, Three-Dimensional
PubMed: 37758947
DOI: 10.1038/s41586-023-06569-5 -
Neuron Dec 2023Leptomeninges, consisting of the pia mater and arachnoid, form a connective tissue investment and barrier enclosure of the brain. The exact nature of leptomeningeal...
Leptomeninges, consisting of the pia mater and arachnoid, form a connective tissue investment and barrier enclosure of the brain. The exact nature of leptomeningeal cells has long been debated. In this study, we identify five molecularly distinct fibroblast-like transcriptomes in cerebral leptomeninges; link them to anatomically distinct cell types of the pia, inner arachnoid, outer arachnoid barrier, and dural border layer; and contrast them to a sixth fibroblast-like transcriptome present in the choroid plexus and median eminence. Newly identified transcriptional markers enabled molecular characterization of cell types responsible for adherence of arachnoid layers to one another and for the arachnoid barrier. These markers also proved useful in identifying the molecular features of leptomeningeal development, injury, and repair that were preserved or changed after traumatic brain injury. Together, the findings highlight the value of identifying fibroblast transcriptional subsets and their cellular locations toward advancing the understanding of leptomeningeal physiology and pathology.
Topics: Mice; Animals; Meninges; Arachnoid; Pia Mater; Choroid Plexus; Brain
PubMed: 37776854
DOI: 10.1016/j.neuron.2023.09.002 -
Nature Nov 2023Establishing how neural function emerges from network properties is a fundamental problem in neuroscience. Here, to better understand the relationship between the...
Establishing how neural function emerges from network properties is a fundamental problem in neuroscience. Here, to better understand the relationship between the structure and the function of a nervous system, we systematically measure signal propagation in 23,433 pairs of neurons across the head of the nematode Caenorhabditis elegans by direct optogenetic activation and simultaneous whole-brain calcium imaging. We measure the sign (excitatory or inhibitory), strength, temporal properties and causal direction of signal propagation between these neurons to create a functional atlas. We find that signal propagation differs from model predictions that are based on anatomy. Using mutants, we show that extrasynaptic signalling not visible from anatomy contributes to this difference. We identify many instances of dense-core-vesicle-dependent signalling, including on timescales of less than a second, that evoke acute calcium transients-often where no direct wired connection exists but where relevant neuropeptides and receptors are expressed. We propose that, in such cases, extrasynaptically released neuropeptides serve a similar function to that of classical neurotransmitters. Finally, our measured signal propagation atlas better predicts the neural dynamics of spontaneous activity than do models based on anatomy. We conclude that both synaptic and extrasynaptic signalling drive neural dynamics on short timescales, and that measurements of evoked signal propagation are crucial for interpreting neural function.
Topics: Animals; Caenorhabditis elegans; Calcium; Models, Neurological; Mutation; Neural Pathways; Neurons; Neuropeptides; Synapses; Signal Transduction
PubMed: 37914938
DOI: 10.1038/s41586-023-06683-4 -
Topics in Current Chemistry (Cham) Dec 2023While bioorthogonal reactions are routinely employed in living cells and organisms, their application within individual organelles remains limited. In this review, we... (Review)
Review
While bioorthogonal reactions are routinely employed in living cells and organisms, their application within individual organelles remains limited. In this review, we highlight diverse examples of bioorthogonal reactions used to investigate the roles of biomolecules and biological processes as well as advanced imaging techniques within cellular organelles. These innovations hold great promise for therapeutic interventions in personalized medicine and precision therapies. We also address existing challenges related to the selectivity and trafficking of subcellular dynamics. Organelle-targeted bioorthogonal reactions have the potential to significantly advance our understanding of cellular organization and function, provide new pathways for basic research and clinical applications, and shape the direction of cell biology and medical research.
Topics: Organelles; Cell Biology
PubMed: 38103067
DOI: 10.1007/s41061-023-00446-5 -
Advances in Physiology Education Sep 2023In the field of anatomy education, the debate over the superiority of learning with or without human donors is decades long and ongoing. Arguments for or against the use... (Review)
Review
In the field of anatomy education, the debate over the superiority of learning with or without human donors is decades long and ongoing. Arguments for or against the use of human donors in anatomy education vary, depending on the healthcare discipline. Physical therapy programs have been particularly resistant to the trend away from the use of human donors. In this personal view, I present my history of anatomy education and how my perspectives on teaching and learning anatomy have changed dramatically throughout my teaching experiences. The purpose of this article is to support instructors who are creating anatomy courses for all healthcare trainees without donors, inspire those teaching with donors to incorporate other methods of instruction and evaluation, challenge educators to examine their own biases surrounding anatomy education, and provide recommendations for developing an anatomy course without human donors. Included in this article is the perspective of a practicing physical therapist who learned through human dissection and has assisted me in the development and management of the human anatomy course in our physical therapy curriculum. This article provides an overview of how to design an anatomy course without anatomical donors for doctor of physical therapy students and includes recommendations for instructors who need to reduce or eliminate anatomical donors from their anatomy curriculum.
Topics: Humans; Anatomists; Anatomy; Cadaver; Curriculum; Dissection; Education, Medical, Undergraduate; Educational Status; Learning; Students, Medical; Teaching
PubMed: 37141435
DOI: 10.1152/advan.00004.2023 -
Annals of Botany Oct 2023Pseudanthia or 'false flowers' are multiflowered units that resemble solitary flowers in form and function. Over the last century the term 'pseudanthium' has been... (Review)
Review
BACKGROUND
Pseudanthia or 'false flowers' are multiflowered units that resemble solitary flowers in form and function. Over the last century the term 'pseudanthium' has been applied to a wide array of morphologically divergent blossoms, ranging from those with easily noticeable florets to derived, reduced units in which individual flowers become almost indistinguishable. Although initially admired mostly by botanists, the diversity and widespread distribution of pseudanthia across angiosperms has already made them a fascinating topic for evolutionary and developmental comparative studies.
SCOPE
This review synthesizes historical and current concepts on the biology of pseudanthia. Our first aim is to establish a clear, operational definition of pseudanthium and disentangle common terminological misconceptions surrounding that term. Our second aim is to summarize knowledge of the morphological and developmental diversity of pseudanthia and embed it within a modern phylogenetic framework. Lastly, we want to provide a comprehensive overview on the evolution and ecological importance of pseudanthia and outline perspectives for future studies.
CONCLUSIONS
The understanding of pseudanthia has changed multiple times and reflects three different interpretations of their 'flower-like' qualities: developmental (similarity in structure), figural (similarity in form and function) and phylogenetic (homology between angiosperm flowers and monoecious reproductive shoots in gymnosperms). Here, we propose to narrow the term pseudanthium to multiflowered blossoms resembling zoophilous flowers in form, i.e. in being structurally subdivided in a showy periphery and a reproductive centre. According to this definition, pseudanthia sensu stricto evolved independently in at least 41 angiosperm families. The recurrent acquisition of pseudanthia sensu stricto in all major lineages of flowering plants indicates repeated interactions between developmental constraints (smallness of flowers, meristematic conditions) and selective pressures, such as demands of pollinators and/or environmental conditions.
Topics: Humans; Magnoliopsida; Phylogeny; Flowers; Reproduction; Biological Evolution
PubMed: 37478306
DOI: 10.1093/aob/mcad103 -
Revista Da Associacao Medica Brasileira... 2023
Topics: Female; Humans; Hand
PubMed: 37556627
DOI: 10.1590/1806-9282.2023S108 -
Biology Open Aug 2023This review highlights the largely understudied behavior of gliding locomotion, which is exhibited by a diverse range of animals spanning vertebrates and invertebrates,... (Review)
Review
This review highlights the largely understudied behavior of gliding locomotion, which is exhibited by a diverse range of animals spanning vertebrates and invertebrates, in air and in water. The insights in the literature gained from January 2022 to December 2022 continue to challenge the previously held notion of gliding as a relatively simple form of locomotion. Using advances in field/lab data collection and computation, the highlighted studies cover gliding in animals including seabirds, flying lizards, flying snakes, geckos, dragonflies, damselflies, and dolphins. Altogether, these studies present gliding as a sophisticated behavior resulting from the interdependent aspects of morphology, sensing, environment, and likely selective pressures. This review uses these insights as inspiration to encourage researchers to revisit gliding locomotion, both in the animal's natural habitat and in the laboratory, and to investigate questions spanning gliding biomechanics, ecology, sensing, and the evolution of animal flight.
Topics: Animals; Odonata; Wings, Animal; Locomotion; Flight, Animal; Biomechanical Phenomena; Lizards
PubMed: 37581305
DOI: 10.1242/bio.059973 -
European Journal of Cell Biology Dec 2023
Topics: Plants; Cell Biology; Plant Cells
PubMed: 37596137
DOI: 10.1016/j.ejcb.2023.151345